A School-Based Study of Irritable Bowel Syndrome in Medical Students in Beijing, China: Prevalence and Some Related Factors

Purpose. To investigate the prevalence and some related factors about irritable bowel syndrome (IBS) in medical students. Methods. A cross-sectional study was carried out from February 2014 to Jun 2014 in Beijing University of Chinese Medicine, Beijing, China. All participants were asked to completed self-administered questionnaires. Results. Seven hundred and sixty-seven medical students (23.26 ± 2.88 years, 25.6% males) completed the survey. The prevalence of IBS was 33.3%, with a high prevalence in women (36.1%). Among the IBS patients, 112 cases were IBS-M (43.9%) and 77.6% had moderately severe IBS. There were no statistical differences between control group and IBS patients in anxiety and depression scores (P > 0.05). The total score of Pittsburgh sleep quality index (PSQI) was significantly higher for medical students with IBS and 35.5% of IBS patients had severe sleep disorder; the scores of child trauma questionnaire (CTQ) and student-life stress inventory (SLSI) were also higher in IBS patients. Sex and sleep disorder were independently associated with IBS (OR, 1.914, 95%CI, 1.281–2.860; OR, 1.143, 95%CI, 1.074–1.216). Conclusion. Our study has many valuable findings and they may provide valuable suggestions for the necessary intervention and treatment measures towards medical students.


Introduction
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder, characterized by abdominal pain or discomfort in association with altered bowel habits [1]. IBS is common in the general population; the prevalence of this disease in European countries was about 20%; in recent years, the morbidity of Asian countries is rising year by year, which is near to that in Western countries [2][3][4][5]. Without any biological markers, the diagnosis of IBS mainly depends on the patient's symptoms. According to Rome III criteria, IBS patients were subdivided into diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C), mixed type IBS (IBS-M), and unsubtyped IBS (IBS-U) [6].
Although the pathophysiology of IBS is unclear, gender, diet, lifestyle, psychiatric disorders, sleep problems, early adverse life events (EALs), and stress have been considered as risk factors to IBS, but they are controversial [3][4][5][7][8][9][10][11][12][13][14][15]. Medical students are a special group, characterized by tremendous cognitive and emotional changes. At the same time, due to massive study and exams load, increasing fierce competition for jobs, undesirable living, and eating habits, medical students may be an especially high-risk population for IBS [3]. In recent years, the number of IBS research papers, relating to medical students, has increased in China and the rest of the world [3][4][5]16]; however, to the best of our knowledge, no comprehensive survey (including prevalence, diet, lifestyle, psychiatric disorders, sleep problems, EALs, and stress) about IBS using Rome III criteria has been carried out on medical students in Beijing, China, nowadays. The information about prevalence and related factors in medical students may provide targeted recommendations for the treatment of IBS, which can effectively improve the clinical symptoms of IBS patients and enhance their learning efficiency and quality of life.
So the aims of this study were (1) to investigate the prevalence of IBS in medical students according to Rome III criteria and the related factors with IBS and (2) to evaluate the risk factors associated with the disorder.

Study Setting and Ethics Statement.
This cross-sectional study was carried out from February 2014 to June 2014 in Beijing University of Chinese Medicine, Beijing, China. All participants gave their written informed consent prior to completing self-administered questionnaires. The study protocol was approved by the ethics committee of the China-Japan friendship hospital, Beijing, China.

Participants.
This study included medical students from the first to the seventh year, and we employed a multistage stratified random sample method [4,8]. Using the following formula, = /( / ) 2 = 2 × / 2 , where = 1.96 (error of the first kind), = 20% (estimated prevalence), = 1 − , and = 15% × (permissive error), the expected minimal sample size for this study was 683. According to the 90% response rate, the number of students should be 759. To ensure reliability, we proceeded to recruit 843 medical students into the study.

Criteria of Exclusion.
Subjects with self-reported organic gastrointestinal disorder, family history of cancer, weight loss, anemia, bloody stools, abnormal laboratory findings, other alarming signs, and those who had previously undergone gastrointestinal surgery were excluded from our study [1].

Personal General Information, Lifestyle, and Eating
Habits. Personal data, such as sex, age, height, weight, and lifestyle and eating habits, such as exercise frequency, smoking, and alcohol consumption, were included in the questionnaire. With the grade, low means the students from the first to the fourth year, and high means from the fifth to the seventh year.

Chinese Version of Rome III Criteria for Diagnosis of IBS.
The Chinese version of Rome III criteria for diagnosis of IBS has been widely used [1,17,18]. The diagnosis of IBS was based on the presence of abdominal pain or discomfort which had to occur at least 3 days per month for at least three months during the previous six months, with at least two or more of the following conditions: symptoms associated with a change in frequency or form of stool and pain improved after defecation. Patients with IBS were divided into diarrheapredominant IBS (IBS-D), constipation-predominant IBS (IBS-C), mixed IBS (IBS-M), and unsubtyped IBS (IBS-U) according to the proportion of hard and lumpy stools.

"Severity of IBS"
Questionnaire. The IBS severity questionnaire includes five items: the severity of perceived pain, the presence and severity of abdominal distension, the frequency of abdominal pain or discomfort, satisfaction with bowel habits, and the quantification of interference in the patient's general lifestyle by these symptoms. Each item has a 100-point scale from 20 to 100 score and the total severity score is the sum of the five items. Patients were classified as having mild IBS (IBS severity score 75-175), moderately severe IBS (score 175-300), and severe IBS (score > 300) [19,20].

Pittsburgh Sleep Quality Index (PSQI).
PSQI is a 19item, self-administered questionnaire [21]. It has been widely used to assess the sleep quality of subjects [8]. The contents of the PSQI include seven items: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep inducers, and daytime dysfunction. Each item uses a three-point response scale, the total score was used to calculate the PSQI global index (ranging from 0 to 21); a total score > 5 means poor sleepers, and when the total score is up to or greater than 8, it means a severe sleep disorder.

Child Trauma Questionnaire (CTQ)
. CTQ, which has 28 items, was developed by Bernstein et al. [22]. CTQ consists of five subscales (emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect, each subscale has five items) to evaluate the degree of child trauma (one type of EALs) and three items for validity evaluation. Each item has a 5-point scale from 1 to 5 score; the total score ranges from 25 to 125 [23]. [24]. SLSI has 51 items with five stress categories (frustration, conflicts, pressures, changes, and self-imposed) and four categories of reactions to stressors. Each item uses a 5-point scale; the total score is the sum of the nine categories. The purpose of the SLSI was to assess the mean responses to different stressors and reactions to stressors among students [24].

Statistical
Analysis. Statistical analysis was performed using the SPSS version 19.0 (IBM Corporation, NY, USA). Categorical variables were analyzed by Pearson's 2 or Fisher's exact test. The -test was used to compare group differences for continuous variables; data is presented as mean ± SD. Logistic regression analysis was used to assess the possible risk factors. The odds ratio (OR) with a 95% confidence  (Table 3). However, for females, IBS patients had a higher score than healthy controls in anxiety (4.83 ± 2.67 versus 4.23 ± 2.85, = 0.015).
As shown in Table 3, the total score of the PSQI was significantly higher for medical students with IBS than for those without IBS; on the other hand, for females, the score was 6.65 ± 2.67 in IBS cases and 5.42 ± 2.73 in controls ( < 0.001); for males, the scores were 5.96 ± 2.38 and 4.97 ± 2.45 ( = 0.014). According to the PSQI score standard, the prevalence of severe sleep disorder was 35.5% in IBS patients and 17.8% in subjects without IBS. Table 4 illustrates that the score of emotional neglect was much higher in IBS patients ( = 0.045); the other 4 subscales and the total score of CTQ were also higher in IBS group, but there were no significant differences.

CTQ and SLSI Scores in IBS and Control Groups.
For SLSI, the total score of SLSI and the other seven categories showed statistical differences between IBS and control groups (Table 5). Similar results were obtained in females (Table 6); however, for males, no differences were found in the total score of SLSI and nine categories between IBS patients and health group.

Risk Factors for IBS.
After the univariate analysis, to find independent risk factors for IBS, multivariable logistic regression analysis was performed. Sex and sleep disorder were independently associated with IBS (Table 7). Table 7 shows the evaluation of risk factors for irritable bowel syndrome by multivariate logistic regression analysis.

Discussion
To our knowledge, this was the first comprehensive survey using the Rome III criteria to assess the prevalence of some    related factors in medical students in Beijing, China. In this study, the prevalence of IBS in medical students was 33.3%, 43.9% of those with IBS had IBS-M, and the majority of the patients (77.6%) had moderately severe IBS. IBS patients had a significantly higher PSQI score together with a 35.5% prevalence of severe sleep disorder. In the assessments of CTQ and SLSI, the scores in patients were also higher. Our survey suggests that medical students have an even higher prevalence of IBS, more female students suffered from IBS, and gender may be a risk factor of this disease. The results are in line with that in previous studies [3,4]. Considering the special living environment (countless examinations and heavy clinical practice in hospital) together with lacking the ability of self-adjustment and adaptation, medical students may be an especially high-risk population for IBS. At the same time, we found that female students had a higher prevalence than male students, speculating that the difference of hormone levels may play a role [25]. In addition, women are more likely to have mental problems and sleep disorders, which may be related to the high prevalence of IBS. For females, the students with low grade had a higher prevalence of IBS, which is contrary to the previous study [4]. Differences in study groups and evaluation standard may explain the relative lacking of medical knowledge; low health care seeking rate may also give rise to the high prevalence of IBS.
Unfortunately, in the survey about eating habits and lifestyles, we only found significant difference in seafood diet between IBS and control groups; IBS patients had a lower frequency in this item. It may be true that some IBS patients had food intolerance. Gastrointestinal symptoms appeared after eating seafood, which made them artificially eliminate the seafood diet later.
In our survey, no statistical differences were found between IBS patients and controls in anxiety and depression scores. However, in the subgroup analysis, female patients had obviously higher score in anxiety score, which is similar to a recent study from Pakistan [3]. Studies have shown that, compared to healthy controls, 40%-60% of IBS patients with obvious mental abnormalities and early relieving mental disorders might be useful for an effective management of IBS [10,26]. Psychosocial factors can lead to dysfunction of the brain-gut axis, which in turn causes dysfunction of the gut through neural, neuroimmune, and neuroendocrine pathways [27].
To date, no study has been conducted to explore the association between IBS and sleep disorder in medical students in China. From our data, the total score of the PSQI was significantly higher for medical students with IBS than for those without IBS, and the prevalence of severe sleep disorder was 35.5% in IBS group. Sleep disorder was independently associated with IBS. A study from China found that 34.3% of the middle school students had sleep problems, and poor sleep was independently associated with IBS [8]. It has been demonstrated that poor sleep is a dangerous stress factor, which can seriously influence the  cognition, emotion, somatic reaction, and gastrointestinal function [28]. A population-based study showed that sleep disorder was associated with increased odds for multiple gastrointestinal symptoms [29]. Studies have shown that poor sleep can change the intestinal sensitivity, which increases the patient's perception of clinical symptoms [29,30]. Disruption of the normal biological rhythm may lead to alteration in visceral motility and sensitivity, thus changing the colonic physiological function of the gut. Epidemiologic studies have found an increased prevalence of EALs in IBS patients [14,31].
In our study, we have shown that the score of emotional neglect was much higher in IBS patients.
It is the first research using the CTQ questionnaire to investigate the relationships between EALs and IBS in medical students. In USA, more than 60% adults reported that they had at least one EAL before the age of 18 [32]. EALs may cause the disturbance of central nerve system including hypothalamic-pituitary-adrenal (HPA) axis, cognitive behavior, autonomic responsiveness, and emotional regulation, thus participating in the occurrence and development of IBS [14]. The other 4 subscales and the total score of CTQ were also higher in IBS group, but there were no significant differences. We speculate that, with expansion of the sample size, the result may be different.
In the present study, SLSI scores were significantly increased in patients with IBS and this phenomenon is more pronounced in women. However, there were no statistical differences in males. To our knowledge, this was the first investigation using the SLSI to assess the relationships between stress factors and IBS in medical students. In recent years, increasing evidence supports the role of stress in the pathophysiology of IBS [13,15]. The effects of stress on functions of gut are universal, and the major effects of stress on gastrointestinal tract include alteration in gastrointestinal motility and visceral perception, increase in intestinal permeability, changes in intestinal endocrine, negative effect of intestinal mucosal blood flow, and negative effects on intestinal microbiota [13]. Differences in the following factors between women and men may explain why our findings were not the same in gender about the SLSI scores: hormone level, social role and health care seeking behavior, and physiological and psychological reactions together with coping styles when exposed to stressors. The strength of this research was the high questionnaire responses and enough sample size to ensure the credibility of our findings. Also, we have some limitations. First, the survey was restricted to medical students, which might influence the generalizability of our results. Second, the study was based on self-reporting questionnaires, without using gastrointestinal endoscopy to exclude structural intestinal diseases; sometimes, it is unpractical in a cross-sectional survey with a large sample.

Conclusion
We conclude from this cross-sectional study that the prevalence of IBS in medical students is 33.3%, the scores of CTQ and SLSI were also higher in IBS patients, and sex and sleep disorder were independently associated with IBS. It may provide valuable suggestions for the necessary intervention and treatment measures towards medical students; too much attention was given just to the intestinal symptoms formerly. Further prospective studies evaluating the definite pathological mechanisms should be carried out.